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Updated: Jun 27, 2026

Generating De Novo Antigen-specific Human T Cell Receptors by Retroviral Transduction of Centric Hemichain
Published on: October 25, 2016
Engineering a Second Interchain Disulfide Bond in the αβ T-Cell Receptor Constant Domain: A Powerful Strategy to
Nguyen Trung Quan1, Xiangliang Lin2, Duong Thi Nhu Xuan3
1Department of Biomedical Sciences, City University of Hong Kong, Kowloon, Hong Kong 999077, China.
Abstract:
Adoptive TCR-T cell therapy holds great promise for personalised cancer treatment, yet it is limited by poor surface expression, chain mispairing, and suboptimal stability of introduced TCRs. One effective structure-guided approach is to introduce a second interchain disulfide bond between the α and β constant domains. This review summarises the structural and mechanistic basis of this strategy, its impact on TCR folding, CD3 assembly, mechanotransduction, and anti-tumour function, as well as current engineering approaches, persistent challenges, and future perspectives. Preclinical studies demonstrate improved heterodimer stability, reduced mispairing, higher surface expression, and enhanced signalling, positioning the second disulfide bond as a valuable complementary tool in next-generation TCR engineering.
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